Zhang Lian, Schroeder Stephanie, Fong Nova, Bentley David L
Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, UCHSC at Fitzsimons, Aurora, CO 80045, USA.
EMBO J. 2005 Jul 6;24(13):2379-90. doi: 10.1038/sj.emboj.7600711. Epub 2005 Jun 9.
We report that under 'transcriptional stress' in budding yeast, when most pol II activity is acutely inhibited, rapid deposition of nucleosomes occurs within genes, particularly at 3' positions. Whereas histone H3K4 trimethylation normally marks 5' ends of highly transcribed genes, under 'transcriptional stress' induced by 6-azauracil (6-AU) and inactivation of pol II, TFIIE or CTD kinases Kin28 and Ctk1, this mark shifted to the 3' end of the TEF1 gene. H3K4Me3 at 3' positions was dynamic and could be rapidly removed when transcription recovered. Set1 and Chd1 are required for H3K4 trimethylation at 3' positions when transcription is inhibited by 6-AU. Furthermore, Deltachd1 suppressed the growth defect of Deltaset1. We suggest that a 'transcriptional stress' signal sensed through Set1, Chd1, and possibly other factors, causes H3K4 hypermethylation of newly deposited nucleosomes at downstream positions within a gene. This response identifies a new role for H3K4 trimethylation at the 3' end of the gene, as a chromatin mark associated with impaired pol II transcription.
我们报道，在芽殖酵母的“转录应激”状态下，当大多数聚合酶II（pol II）活性被急性抑制时，核小体在基因内迅速沉积，特别是在3'端位置。正常情况下，组蛋白H3K4三甲基化标记高转录基因的5'端，但在由6-氮杂尿嘧啶（6-AU）诱导的“转录应激”以及pol II、TFIIE或CTD激酶Kin28和Ctk1失活的情况下，该标记转移到了TEF1基因的3'端。3'端位置的H3K4Me3是动态的，当转录恢复时可迅速去除。当转录被6-AU抑制时，Set1和Chd1是3'端位置H3K4三甲基化所必需的。此外，缺失Chd1可抑制缺失Set1的生长缺陷。我们认为，通过Set1、Chd1以及可能的其他因子感知到的“转录应激”信号，会导致基因内下游位置新沉积核小体的H3K4超甲基化。这种反应确定了基因3'端H3K4三甲基化的一个新作用，即作为与pol II转录受损相关的染色质标记。
